Adipose tissue demonstrates considerable plasticity and heterogeneity, enabling metabolic, cellular and structural adaptations to environmental signals. This adaptability is key for maintaining metabolic homeostasis. Impaired adipose tissue plasticity can lead to abnormal adipose tissue responses to metabolic cues, which contributes to the development of cardiometabolic diseases. In chronic obesity, white adipose tissue undergoes pathological remodelling marked by adipocyte hypertrophy, chronic inflammation and fibrosis, which are linked to local and systemic insulin resistance. Research data suggest that the capacity for healthy or unhealthy white adipose tissue remodelling might depend on the intrinsic diversity of adipose progenitor cells (APCs), which sense and respond to metabolic cues. This Review highlights studies on APCs as key determinants of adipose tissue plasticity, discussing differences between subcutaneous and visceral adipose tissue depots during development, growth and obesity. Modulating APC functions could improve strategies for treating adipose tissue dysfunction and metabolic diseases in obesity.

The body weight following bariatric surgery is a primary concern for both healthcare professionals and surgical candidates. However, it remains unclear whether variations in preoperative fat distribution influence weight loss outcomes.

The aim of this study was to evaluate the effect of abdominal fat distribution on postoperative weight loss and body mass index (BMI) reduction, and to clarify the role of different fat depots in weight loss outcomes.

Preoperative data from patients with overweight or obesity, along with their weight records at 1, 2 and 5 years following surgery, were retrospectively collected. Multiple levels of abdominal fat areas were measured using computerized tomography imaging. Statistical analyses included Pearson's correlation coefficients, multiple linear regressions, ridge regressions, decision tree regressions and paired t tests to evaluate the associations and influences.

A total of 139 patients were initially included. The statistical analysis results indicated that umbilical subcutaneous adipose tissue (SAT) was an independent factor influencing weight and BMI loss at the 1-year follow-up (n = 67, p < 0.01). Furthermore, umbilical SAT demonstrated significant correlations with sustained BMI reduction over the long term.

Umbilical SAT is a significant factor in postoperative weight and BMI loss. Patients with greater SAT may experience more substantial weight and BMI reductions following surgery, offering new insights into personalized weight loss strategies and alternative approaches for assisted weight loss.

Precision medicine is still not considered as a standard of care in obesity treatment, despite a large heterogeneity in the metabolic phenotype of individuals with obesity. One of the strongest factors influencing the variability in metabolic disease risk is adipose tissue (AT) dysfunction; however, there is little understanding of the link between distinct cell populations, cell-type-specific transcriptional programs, and disease severity. Here, we generated a comprehensive cellular map of subcutaneous and visceral AT of individuals with metabolically healthy and unhealthy obesity. By combining single-nucleus RNA-sequencing data with bulk transcriptomics and clinical parameters, we identified that mesothelial cells, adipocytes, and adipocyte-progenitor cells exhibit the strongest correlation with metabolic disease. Furthermore, we uncovered cell-specific transcriptional programs, such as the transitioning of mesothelial cells to a mesenchymal phenotype, that are involved in uncoupling obesity from metabolic disease. Together, these findings provide valuable insights by revealing biological drivers of clinical endpoints.

Cardiovascular diseases (CVDs) remain a global health concern, prompting ongoing research into novel contributors to their pathogenesis. Due to the proximity of the coronary arteries and the myocardium in epicardial adipose tissue (EAT) and pericardial adipose tissue (PAT), these tissues have emerged as key areas of interest for their potential influence on cardiac function and vascular health. This review synthesizes current research on the physiological and biological characteristics of EAT and PAT, exploring their composition and clinical measurement approaches. The roles of EAT and PAT in coronary artery disease (CAD), atrial fibrillation, and heart failure are discussed, and the contributions of EAT and PAT to these cardiovascular conditions are highlighted alongside their potential as therapeutic targets.

A comparative transcriptomic analysis in adipose stem and progenitor cells (ASPCs) between obese and lean mice might facilitate the identification of novel adipogenic genes. Here, we compare transcriptomic differences in the ASPCs of subcutaneous adipose tissue (SAT) between the mice fed on a high-fat-diet (HFD) and the chow diet (CD)-fed mice by analyzing three independent single-cell RNA sequencing datasets. Six differential genes, including three up-regulated genes Aspn, Rrbp1, Fbln2 and three down-regulated genes Htra1, Plpp3, Efemp1, are identified and confirmed in HFD-fed mice. Further, the expression of these genes is found to be significantly diminished in the differentiated 3T3-L1 cells. Treatment with luteolin, a dietary flavonoid known to inhibit 3T3-L1 adipogenesis, reverses the decreased expression of Aspn, Htra1 and Efemp1. Furthermore, knockdown of Aspn, Htra1 and Efemp1 significantly facilitates 3T3-L1 adipogenesis. Together, these genes not only are differential in ASPCs between obese and lean mice, but also are the adipogenic inhibitory genes that can be up-regulated by luteolin treatment.

Recent studies have found that tobacco smoking is associated with fat distribution, yet limited research has focused on its relationship with visceral adipose tissues (VATs). Furthermore, the cellular and molecular mechanisms underlying the interactions among smoking, epigenetic modifications, and VATs remain unknown.

We performed univariable Mendelian randomization (MR) analysis to elucidate the causal relationship between smoking behaviours and VATs, including epicardial and pericardial adipose tissue (EPAT), liver fat (LF), and pancreas fat (PF). This approach could minimize the impact of confounders and reverse causality through utilizing genetic variants to proxy the smoking behaviours. Mediation MR analysis were conducted to detect potential mediators. Additionally, summary-data-based MR (SMR) and colocalization analysis were performed to explore the association between smoking-related DNA methylation and VATs.

We identified a convincing association between smoking initiation and increased EPAT (beta: 0.15, 95% CI: 0.06, 0.23, p = 7.01 × 10-4) and LF area (beta: 0.15, 95% CI = 0.05, 0.24, p = 2.85 × 10-3), respectively. Further mediation analysis suggested type 2 diabetes mellitus (T2DM) as a potential mediator within these co-relationships. When further exploring the associations between the smoking related DNA methylation and VATs, we identified that WT1 methylation at cg05222924 was significantly linked to a lower EPAT area (beta: -0.12, 95% CI: -0.16, -0.06, PFDR = 2.24 × 10-3), while GPX1 methylation at cg18642234 facilitated the deposition of EPAT (beta: 0.15, 95% CI: 0.10, 0.20, PFDR = 1.66 × 10-4).

Our study uncovered a significant causal effect between smoking and VATs, with T2DM identified as a potential mediator. Further investigation into DNA methylation yielded novel insights into the pathogenic role of smoking on EPAT.

The aim of this study was to investigate the relationships between imaging indicators of obesity, as measured by computed tomography (CT), and clinical outcomes at 90 days and 1 year after emergent endovascular therapy (EVT).

Participants with emergent large vessel occlusion (ELVO) who underwent EVT were prospectively enrolled. During hospitalization, CT scans were performed to evaluate the visceral adipose tissue area (VATA) and skeletal muscle area (SMA) at the level of the third lumbar spine. Multivariate regression analysis was used to assess the correlation of obesity-related imaging measures with various outcomes: mortality, favorable functional outcomes (modified Rankin scale (mRS) score 0-2), and functional improvement (shift in mRS score) at 90 days and 1 year.

A total of 306 ELVO patients were included in the study, with a median age of 64 years and a median baseline National Institutes of Health Stroke Scale (NIHSS) score of 18. After adjusting for potential confounders, the VATA-to-SMA ratio (VSR) was significantly associated with a favorable functional outcome (OR 0.30, 95% CI 0.13 to 0.70) at 90 days and a favorable functional outcome (OR 0.27, 95% CI 0.12 to 0.61) and functional improvement (OR 0.33, 95% CI 0.12 to 0.92) at the 1 year follow-up.

Our study indicated that lower VSR levels are associated with favorable functional outcomes, along with functional improvement at 90 days and 1 year of follow-up.

Among people with abdominal obesity, women are more likely to develop diabetes than men. Mobile health (mHealth)-based technologies provide the flexibility and resource-saving opportunities to improve lifestyles in an individualized way. However, mHealth-based diabetes prevention programs tailored for busy mothers with abdominal obesity have not been reported yet.

The aim of this study is to evaluate the feasibility and acceptability of an mHealth-based diabetes prevention program and its preliminary efficacy in reducing weight-related variables, behavioral variables, psychological variables, and diabetes risk among Chinese mothers with abdominal obesity over 6 months.

A randomized controlled trial was conducted at health management centers in 2 tertiary hospitals in Changsha, China. The mHealth group (n=40) received 12 weekly web-based lifestyle modification modules for diabetes prevention, 6 biweekly individualized health education messages based on their goal settings, and a Fitbit tracker. The control group (n=40) received 12 weekly web-based general health education modules, 6 biweekly general health education messages, and a Fitbit tracker. Data were collected at baseline, 3 months, and 6 months on the feasibility and acceptability outcomes, weight-related variables (waist circumference and BMI), diabetes risk scores, glycemic levels, behavioral variables (daily step count, active minutes, fruit and vegetable intake, calorie consumption, and sleep duration), and psychological variables (self-efficacy and social support for physical activity and diet, perceived stress, and quality of life). Generalized estimating equations were used for data analysis.

Approximately 85% (68/80) of the participants completed 6 months of follow-up assessments. Regarding the feasibility and acceptance of the program in the mHealth group, the average number of modules reviewed was 7.9 out of 12, and the satisfaction score was 4.37 out of 5. Significant improvements at 6 months between the intervention and control groups were found in waist circumference (β=-2.24, 95% CI -4.12 to -0.36; P=.02), modifiable diabetes risk scores (β=-2.5, 95% CI -4.57 to -0.44; P=.02), daily steps (β=1.67, 95% CI 0.06-3.29; P=.04), self-efficacy for physical activity (β=1.93, 95% CI 0.44-3.43; P=.01), social support for physical activity (β=2.27, 95% CI 0.80-3.74; P=.002), and physical health satisfaction (β=0.82, 95% CI 0.08-1.55; P=.03). No differences were found in BMI, total diabetes risk score, daily active minutes, daily intake of fruits and vegetables, sleep duration, daily calorie consumption, self-efficacy, and social support for diet (P>.05).

This study addresses the potential role of tailored lifestyle interventions based on mHealth technology by offering tailored web-based health modules and health information in managing diabetes risk among mothers with abdominal obesity. The mHealth diabetes prevention program provides a flexible, customized, and resource-saving model for busy mothers. Future research could further explore the efficacy improvement on dietary behaviors to better serve the health care needs of this population.

Chinese Clinical Trial Registry ChiCTR2400090554; https://www.chictr.org.cn/showproj.html?proj=226411.

Recent studies have underscored the metabolic and cardiovascular regulatory capacity of perirenal adipose tissue (PAT), implicating its potential involvement in the pathogenesis of left ventricular hypertrophy (LVH). This investigation aims to assess the relationship between increased PAT mass and LVH, while also examining the potential mediating role of insulin resistance in this relationship among individuals with type 2 diabetes mellitus (T2DM).

1112 individuals with T2DM were prospectively recruited for this study. Perirenal fat thickness (PrFT), measured using unenhanced abdominal CT, served as a measure of PAT mass. The triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-c) was computed to assess insulin resistance. LVH was identified as left ventricular mass index (LVMI) >115 g/m² in men or LVMI >95 g/m² in women. The correlations of LVH risk with PrFT and TG/HDL-c were analyzed by weighted binomial logistic regression and restricted cubic splines (RCS) analyses. Furthermore, the mediating role of TG/HDL-c in this relationship was explored using the adjusted mediation analysis.

Participants in the LVH group displayed significantly higher PrFT and TG/HDL-c than the non-LVH group (P < 0.001). Adjusting for confounding factors, the LVMI demonstrated a positive correlation with PrFT (β=0.262, P<0.001) and TG/HDL-c (β=0.206, P<0.001). PrFT and TG/HDL-c emerged as independent variables for LVH, with odds ratios of 1.33 (95%CI:1.24-1.43, P<0.001) and 1.20 (95%CI:1.05-1.36, P=0.006), respectively. Each standard deviation increases in PrFT and TG/HDL-c conferred an additional 240% (P<0.001) and 41% (P=0.006) risk for LVH. A linear correlation of LVH risk with PrFT and TG/HDL-c was observed from RCS analysis (P for nonlinear and overall< 0.001). Moreover, TG/HDL-c mediated 13.4% of the association between PrFT and LVMI, and 8.5% between PrFT and LVH.

Increased PAT accumulation contributes to an independent variable for LVH, with insulin resistance acting as a mediating variable in this relationship.

The prevalence of Alzheimer's disease (AD) among adults has continued to increase over the last two decades, which has sparked a significant increase in research that focuses on the topic of "brain health." While AD is partially determined by a genetic predisposition, there are still numerous pathophysiological factors that require further research. This research requirement stems from the acknowledgment that AD is a multifactorial disease that to date, cannot be prevented. Therefore, addressing and understanding the potential AD risk factors is necessary to increase the quality of life of an aging population. To raise awareness of critical pathways that impact AD progression, this review manuscript describes AD etiologies, structural impairments, and biomolecular changes that can significantly increase the risk of AD. Among them, a special highlight is given to inflammasomes, which have been shown to bolster neuroinflammation. Alike, the role of brain-derived neurotrophic factor, an essential neuropeptide that promotes the preservation of cognition is presented. In addition, the functional role of neurovascular units to regulate brain health is highlighted and contrasted to inflammatory conditions, such as cellular senescence, vascular damage, and increased visceral adiposity, who all increase the risk of neuroinflammation. Altogether, a multifactorial interventional approach is warranted to reduce the risk of AD.

Perivascular adipose tissue (PVAT) is a dynamic tissue that affects vascular function and cardiovascular health. The connection between PVAT, the immune system, obesity, and vascular disease is complex and plays a pivotal role in the pathogenesis of vascular diseases such as atherosclerosis, hypertension, and vascular inflammation. In cardiometabolic diseases, PVAT becomes a significant source of proflammatory adipokines, leading to increased infiltration of immune cells, in cardiometabolic diseases, PVAT becomes a significant source of proinflammatory adipokines, leading to increased infiltration of immune cells, promoting vascular smooth muscle cell proliferation and migrationpromoting vascular smooth muscle cell proliferation and migration. This exacerbates vascular dysfunction by impairing endothelial cell function and promoting endothelial activation. Dysregulated PVAT also contributes to hemodynamic alterations and hypertension through enhanced sympathetic nervous system activity and impaired vasodilatory capacity of PVAT-derived factors. Therapeutic interventions targeting key components of this interaction, such as modulating PVAT inflammation, restoring adipokine balance, and attenuating immune cell activation, hold promise for mitigating obesity-related vascular complications. Lifestyle interventions, pharmacological agents targeting inflammatory pathways, and surgical approaches aimed at reducing PVAT mass or improving adipose tissue function are potential therapeutic avenues for managing vascular diseases associated with obesity and PVAT dysfunction.

Time-restricted feeding (TRF), an intermittent fasting approach involving a shortened eating window within 24 h, has gained popularity as a weight management approach. This review addresses how TRF may favor fat redistribution and the function of the adipose organ. TRF trials (mainly 16:8 model, with a duration of 5-48 weeks) reported a significant weight loss (1.2-10.2%, ~ 1.4-9.4 kg), with a considerable decrease in total fat mass (1.6-21%, ~ 0.5-7 kg) and visceral adipose compartment (VAC, 11-27%) in overweight and obese subjects. Experimental TRF in normal-fed and obesogenic-diet-fed mice and rats (with a fasting duration ranging between 9 and 21 h within 1-17 weeks) reported a significant reduction in body weight (~ 7-40%), total fat mass (~ 17-71%), and intrahepatic fat (~ 25-72%). TRF also improves VAC and subcutaneous adipose compartment (SAC) function by decreasing adipocyte size, macrophage infiltration, M1-macrophage polarity, and downregulating inflammatory genes. In conclusion, beyond its effect on body weight loss, total fat mass, and intrahepatic fat accumulation, TRF favors adipose organ fat redistribution in overweight and obese subjects by decreasing VAC and improving the function of VAC and SAC.

Significant research interest has been focused on beige adipocytes, the activation of which improves glucose and lipid homeostasis, therefore representing new therapeutic opportunities for metabolic diseases. Various Cre/Lox-based strategies have been used to investigate the developmental history of beige adipocytes and how these cells adapt to environmental changes. Despite the significant advancement of our understanding of beige adipocyte biology, much of the molecular insights of the beige adipocyte, including its origin and cell type-specific function, remain to be further illustrated. It has previously been shown that Chrna2 (cholinergic receptor nicotinic alpha 2 subunit) has selective functionality in beige adipocytes. In this study, we explore the Chrna2-Cre-driven reporter expression in mouse beige adipocytes in vivo and in vitro. Our findings indicate that Chrna2-Cre expression is present selectively in multiple locular beige adipocytes in subcutaneous inguinal white adipose tissue (iWAT) and differentiated stromal vascular fraction from iWAT. Chrna2-Cre expression was detected in iWAT of young pups and mice after cold exposure where a significant number of beige adipocytes are present. Chrna2-Cre-driven reporter expression is permanent in iWAT postlabeling and can be detected in the iWAT of adult mice or mice that have been housed extensively at thermoneutrality after cold exposure, even though only "inactive dormant" beige adipocytes are present in these mice. Chrna2-Cre expression can also be increased by rosiglitazone treatment and β-adrenergic activation. This research, therefore, introduces the Chrna2-Cre line as a valuable tool for tracking the development of beige adipocytes and investigating beige fat function.

Given the fast-increasing prevalence of obesity and its comorbidities, it would be critical to improve our understanding of the cell-type level differences between the two key human adipose tissue depots, subcutaneous (SAT) and visceral adipose tissue (VAT), in their depot-specific contributions to cardiometabolic health. We integrated cell-type level RNA- and ATAC-seq data from human SAT and VAT biopsies and cell-lines to comprehensively elucidate transcriptomic, epigenetic, and genetic differences between the two fat depots. We identify cell-type marker genes for tissue specificity and functional enrichment, and show through genome-wide association study (GWAS) and partitioned polygenic risk score (PRS) enrichment analyses that the marker genes upregulated in SAT adipocytes have more prominent roles in abdominal obesity than those of VAT. We also identify SREBF1 , a master transcription factor (TF) of fatty acid synthesis and adipogenesis, as specifically upregulated in SAT adipocytes and present in numerous SAT functional pathways. By integrating multi-omics data from an independent human cohort, we further show that the risk allele carrier status of seven abdominal obesity GWAS variants in the cis region of SREBF1 affects the adipocyte expression of 146 SAT adipocyte marker genes in trans . We replicate this finding independently in the UK Biobank by showing that the partitioned abdominal obesity PRSs of the trans gene sets differ by the regional SREBF1 risk allele carrier status. In summary, we discover the master TF, SREBF1 , driving the SAT adipocyte expression profiles of more than a hundred of adipocyte marker genes in trans , a finding that indicates that human trans genes can be identified by integrating single cell omics with biobank data.

Perirenal adipose tissue (PRAT) has been identified as an important factor in local and general homeostasis of the human body and is especially important in regulating renal and cardiovascular functions. It has also been identified as a crucial risk factor to consider in cardiovascular and renal disorders, malignancies, and various other diseases. Having a concrete idea of the effects of therapeutic interventions on the size and metabolism of the PRAT could prove highly beneficial. This review summarizes what is known about the PRAT and provides a collection of studies on the effects of therapeutic interventions on PRAT and its related diseases. We used papers written on a variety of subjects, mainly concerning adipose tissue and the effects of therapeutic procedures on it. Our main challenge was to excerpt the information specifically related to the PRAT in these papers. These effects vary greatly, from an increase or decrease in mass or size of the PRAT to changes in metabolism and drug residue accumulation. The current studies often fail to consider PRAT as an individual subject of research and only examine the adipose tissue of the entire body as a whole. This leads us to believe this field could benefit greatly from further research.

For a long time, white adipocytes were thought to function as lipid storages due to the sizeable unilocular lipid droplet that occupies most of their space. However, recent discoveries have highlighted the critical role of white adipocytes in maintaining energy homeostasis and contributing to obesity and related metabolic diseases. These physiological and pathological functions depend heavily on the mitochondria that reside in white adipocytes. This article aims to provide an up-to-date overview of the recent research on the function and dysfunction of white adipocyte mitochondria. After briefly summarizing the fundamental aspects of mitochondrial biology, the article describes the protective role of functional mitochondria in white adipocyte and white adipose tissue health and various roles of dysfunctional mitochondria in unhealthy white adipocytes and obesity. Finally, the article emphasizes the importance of enhancing mitochondrial quantity and quality as a therapeutic avenue to correct mitochondrial dysfunction, promote white adipocyte browning, and ultimately improve obesity and its associated metabolic diseases. © 2024 American Physiological Society. Compr Physiol 14:5581-5640, 2024.

The distinct anatomic environment in which adipose tissues arise during organogenesis is a principle determinant of their adult expansion capacity. Metabolic disease results from a deficiency in hyperplastic adipose expansion within the dermal/subcutaneous depot; thus, understanding the embryonic origins of dermal adipose is imperative. Using single-cell transcriptomics throughout murine embryogenesis, we characterized cell populations, including Bcl11b + cells, that regulate the development of dermal white adipose tissue (dWAT). We discovered that BCL11b expression modulates the Wnt signaling microenvironment to enable adipogenic differentiation in the dermal compartment. Subcutaneous and visceral adipose arises from a distinct population of Nefl + cells during embryonic organogenesis, whereas Pi16 + /Dpp4 + fibroadipogenic progenitors support obesity-stimulated hypertrophic expansion in the adult. Together, these results highlight the unique regulatory pathways used by anatomically distinct adipose depots, with important implications for human metabolic disease.

Chronic kidney disease (CKD) represents a significant and escalating global health challenge, with morbidity and mortality rates rising steadily. Evidence increasingly implicates perirenal adipose tissue (PRAT) deposition as a contributing factor in the pathogenesis of CKD. This review explores how PRAT deposition may exert deleterious effects on renal structure and function. The anatomical proximity of PRAT to the kidneys not only potentially causes mechanical compression but also leads to the dysregulated secretion of adipokines and inflammatory mediators, such as adiponectin, leptin, visfatin, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and exosomes. Additionally, PRAT deposition may contribute to renal lipotoxicity through elevated levels of free fatty acids (FFA), triglycerides (TAG), diacylglycerol (DAG), and ceramides (Cer). PRAT deposition is also linked to the hyperactivation of the renin-angiotensin-aldosterone system (RAAS), which further exacerbates CKD progression. Recognizing PRAT deposition as an independent risk factor for CKD underscores the potential of targeting PRAT as a novel strategy for the prevention and management of CKD. This review further discusses interventions that could include measuring PRAT thickness to establish a baseline, managing metabolic risk factors that promote its deposition, and inhibiting key PRAT-induced signaling pathways.

Living organisms store their energy in different forms of fats including lipid droplets, triacylglycerols, and steryl esters. In mammals and some non-mammal species, the energy is stored in adipose tissue which is the innervated specialized connective tissue that incorporates a variety of cell types such as macrophages, fibroblasts, pericytes, endothelial cells, adipocytes, blood cells, and several kinds of immune cells. Adipose tissue is so complex that the scope of its function is not only limited to energy storage, it also encompasses to thermogenesis, mechanical support, and immune defense. Since defects and complications in adipose tissue are heavily related to certain chronic diseases such as obesity, cardiovascular diseases, type 2 diabetes, insulin resistance, and cholesterol metabolism defects, it is important to further study adipose tissue to enlighten further mechanisms behind those diseases to develop possible therapeutic approaches. Adipose organoids are accepted as very promising tools for studying fat tissue development and its underlying molecular mechanisms, due to their high recapitulation of the adipose tissue in vitro. These organoids can be either derived using stromal vascular fractions or pluripotent stem cells. Due to their great vascularization capacity and previously reported incontrovertible regulatory role in insulin sensitivity and blood glucose levels, adipose organoids hold great potential to become an excellent candidate for the source of stem cell therapy. In this review, adipose tissue types and their corresponding developmental stages and functions, the importance of adipose organoids, and the potential they hold will be discussed in detail.

Perivascular adipose tissue (PVAT) is a unique fat depot surrounding blood vessels and plays a vital role in the progression of vascular remodeling and dysfunction. PVAT exhibits remarkable differences in structure, phenotype, origin, and secretome across anatomical locations. The proximity of PVAT to neighboring vascular beds favors a niche for bidirectional communication between adipocytes and vascular smooth muscle cells, endothelial cells, and immune cells. In this review, we update our understanding of PVAT's regional differences and provide a comprehensive exploration of how these differences impact cross-talks between PVAT and the vascular wall. Different PVAT depots show different degrees of vasoprotective function and resilience to pathological changes such as obesity and vasculopathies, shaping multifaceted interactions between PVAT depots and adjacent vasculatures. The depot-specific resilience may lead to innovative strategies to manage cardiometabolic disorders.

Prolonged laparoscopic nephroureterectomy (LNU) for upper tract urothelial cancer (UTUC) can increase the frequency of intravesical recurrence after surgery. Therefore, it is important for urological surgeons to have knowledge on preoperative risk factors for prolonged LNU. However, few studies have investigated the risk factors for prolonged LNU. We hypothesized that the quantity of perirenal fat affects the pneumoretroperitoneum time (PRT) of retroperitoneal LNU (rLNU). This study aimed to investigate the preoperative risk factors for prolonged PRT during rLNU.

We reviewed the data of 115 patients who underwent rLNU for UTUC between 2013 and 2021. The perirenal fat thickness (PFT) observed on preoperative computed tomography (CT) images was used to evaluate the perinephric fat quantity. Preoperative risk factors for PRT during rLNU were analyzed using logistic regression models. The cutoff value for PRT was determined based on the median time.The cutoff values for fat-related factors influencing PRT were defined according to receiver operating characteristic curve analysis.

The median PRT for rLNU was 182 min (interquartile range, 155-230 min). The cutoff values of posterior, lateral, and anterior PFTs were 15 mm, 24 mm, and 6 mm, respectively. Multivariate analysis revealed that a posterior PFT ≥ 15 mm (odds ratio [OR], 2.72; 95% confidence interval, 1.04-7.08; p = 0.0410) was an independent risk factor for prolonged PRT.

Thick posterior PFT is a preoperative risk factor for prolonged PRT during rLNU. For patients with UTUC and thick posterior PFT, surgeons should develop optimal surgical strategies, including the selecting an expert surgeon as a primary surgeon and the selecting transperitoneal approach to surgery or open surgery.

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia, and it significantly increases the risk of cardiovascular complications and morbidity, even with appropriate treatment. Tissue remodeling has been a significant topic, while its systematic transcriptional signature remains unclear in AF.

Our study aims to systematically investigate the molecular characteristics of AF at the cellular-level.

We conducted single-nuclei RNA-sequencig (snRNA-seq) analysis using nuclei isolated from the left atrial appendage (LAA) of AF patients and sinus rhythm. Pathological staining was performed to validate the key findings of snRNA-seq.

A total of 30 cell subtypes were identified among 80, 592 nuclei. Within the LAA of AF, we observed a specific subtype of dedifferentiated cardiomyocytes (CMs) characterized by reduced expression of cardiac contractile proteins (TTN and TRDN) and heightened expression of extracellular-matrix related genes (COL1A2 and FBN1). Transcription factor prediction analysis revealed that gene expression patterns in dedifferentiated CMs were primarily regulated by CEBPG and GISLI. Additionally, we identified a distinct subtype of endothelial progenitor cells (EPCs) demonstrating elevated expression of PROM1 and KDR, a population decreased within the LAA of AF. Epicardial adipocytes disclosed a reduced release of the anti-inflammatory and anti-fibrotic factor PRG4, and an augmented secretion of VEGF signals targeting CMs. Additionally, we noted accumulation of M2-like macrophages and CD8+ T cells with high pro-inflammatory score in LAA of AF. Furthermore, the analysis of intercellular communication revealed specific pathways related to AF, such as inflammation, extracellular matrix, and vascular remodeling signals.

This study has discovered the presence of dedifferentiated CMs, a decrease in endothelial progenitor cells, a shift in the secretion profile of adipocytes, and an amplified inflammatory response in AF. These findings could offer crucial insights for future research on AF and serve as valuable references for investigating novel therapeutic approaches for AF.

Accurate preoperative prediction of the pathological grade of clear cell renal cell carcinoma (ccRCC) is crucial for optimal treatment planning and patient outcomes. This study aims to develop and validate a deep-learning (DL) algorithm to automatically segment renal tumours, kidneys, and perirenal adipose tissue (PRAT) from computed tomography (CT) images and extract radiomics features to predict the pathological grade of ccRCC.

In this cross-ethnic retrospective study, a total of 614 patients were divided into a training set (383 patients from the local hospital), an internal validation set (88 patients from the local hospital), and an external validation set (143 patients from the public dataset). A two-dimensional TransUNet-based DL model combined with the train-while-annotation method was trained for automatic volumetric segmentation of renal tumours, kidneys, and visceral adipose tissue (VAT) on images from two groups of datasets. PRAT was extracted using a dilation algorithm by calculating voxels of VAT surrounding the kidneys. Radiomics features were subsequently extracted from three regions of interest of CT images, adopting multiple filtering strategies. The least absolute shrinkage and selection operator (LASSO) regression was used for feature selection, and the support vector machine (SVM) for developing the pathological grading model. Ensemble learning was used for imbalanced data classification. Performance evaluation included the Dice coefficient for segmentation and metrics such as accuracy and area under curve (AUC) for classification. The WHO/International Society of Urological Pathology (ISUP) grading models were finally interpreted and visualized using the SHapley Additive exPlanations (SHAP) method.

For automatic segmentation, the mean Dice coefficient achieved 0.836 for renal tumours and 0.967 for VAT on the internal validation dataset. For WHO/ISUP grading, a model built with features of PRAT achieved a moderate AUC of 0.711 (95% CI, 0.604-0.802) in the internal validation set, coupled with a sensitivity of 0.400 and a specificity of 0.781. While model built with combination features of the renal tumour, kidney, and PRAT showed an AUC of 0.814 (95% CI, 0.717-0.889) in the internal validation set, with a sensitivity of 0.800 and a specificity of 0.753, significantly higher than the model built with features solely from tumour lesion (0.760; 95% CI, 0.657-0.845), with a sensitivity of 0.533 and a specificity of 0.767.

Automated segmentation of kidneys and visceral adipose tissue (VAT) through TransUNet combined with a conventional image morphology processing algorithm offers a standardized approach to extract PRAT with high reproducibility. The radiomics features of PRAT and tumour lesions, along with machine learning, accurately predict the pathological grade of ccRCC and reveal the incremental significance of PRAT in this prediction.

The correlation of adiponectin and serum tumor necrosis factor alpha (TNFα) with glucometabolic parameters in diabetes mellitus (DM) needs further studies. We aimed in this study to evaluate the relationship between adiponectin and TNFα with glucometabolic parameters in patients with type 2 DM (T2DM).

We conducted a cross-sectional study in the Department of Physiology, College of Medicine, King Saud University, Saudi Arabia. The sample size was 117 from the diabetes clinic of King Abdul-Aziz University hospital through the convenience sampling technique. Subjects were grouped into control (healthy) subjects (53) with no chronic diseases and the diabetic group (64) with confirmed T2DM. Socio-demographic data were collected along with the serum blood sample to analyze the variables.

Adiponectin was significantly high in healthy subjects compared to the diabetic group (control: 14.4 ± 4.3, T2DM: 11.0 ± 4.1, P = 0.000), while TNFα was higher in the T2DM group (7.8 ± 2.7) than in the control group (6.6 ± 2.9, P = 0.024). TNFα was negatively correlated with adiponectin in the control group (-0.279) and in diabetic subjects (-0.311) and positively correlated with HbA1c in the diabetic group (0.319) and triglycerides (0.252). Adiponectin was positively correlated with HDL in the control group (0.252) and in diabetic subjects (0.326). There was an inverse correlation between TNFα and adiponectin.

Adiponectin is higher in healthy subjects than in diabetic patients, while TNFα is higher in diabetic patients. In addition, adiponectin is positively correlated with HDL in healthy as well as diabetic patients. TNFα is positively correlated with HbA1c and triglycerides.

A Wt1 conditional deletion, nuclear red fluorescent protein (RFP) reporter allele was generated in the mouse by gene targeting in embryonic stem cells. Upon Cre-mediated recombination, a deletion allele is generated that expresses RFP in a Wt1-specific pattern. RFP expression was detected in embryonic and adult tissues known to express Wt1, including the kidney, mesonephros, and testis. In addition, RFP expression and WT1 co-localization was detected in the adult uterine stroma and myometrium, suggesting a role in uterine function. Crosses with Wnt7a-Cre transgenic mice that express Cre in the Müllerian duct epithelium activate Wt1-directed RFP expression in the epithelium of the oviduct but not the stroma and myometrium of the uterus. This new mouse strain should be a useful resource for studies of Wt1 function and marking Wt1-expressing cells.

It is now widely understood that visceral adipose tissue (VAT) is a highly active and dynamic organ, with many functions beyond lipid accumulation and storage. In this review, we discuss the immunological role of this tissue, underpinned by the presence of fat-associated lymphoid clusters (FALCs). FALC's distinctive structure and stromal cell composition support a very different immune cell mix to that found in classical secondary lymphoid organs, which underlies their unique functions of filtration, surveillance, innate-like immune responses, and adaptive immunity within the serous cavities. FALCs are important B cell hubs providing B1 cell-mediated frontline protection against infection and supporting B2 cell-adaptative immune responses. Beyond these beneficial immune responses orchestrated by FALCs, immune cells within VAT play important homeostatic role. Dysregulation of immune cells during obesity and aging leads to chronic pathological "metabolic inflammation", which contributes to the development of cardiometabolic diseases. Here, we examine the emerging and complex functions of B cells in VAT homeostasis and the metabolic complications of obesity, highlighting the potential role that FALCs play and emphasize the areas where further research is needed.

Adipose tissue is conventionally recognized as a metabolic organ responsible for storing energy. However, a proportion of adipose tissue also functions as a thermogenic organ, contributing to the inhibition of weight gain and prevention of metabolic diseases. In recent years, there has been significant progress in the study of thermogenic fats, particularly brown adipose tissue (BAT). Despite this progress, the mechanism underlying thermogenesis in beige adipose tissue remains highly controversial. It is widely acknowledged that beige adipose tissue has three additional thermogenic mechanisms in addition to the conventional UCP1-dependent thermogenesis: Ca2+ cycling thermogenesis, creatine substrate cycling thermogenesis, and triacylglycerol/fatty acid cycling thermogenesis. This paper delves into these three mechanisms and reviews the latest advancements in the molecular regulation of thermogenesis from the molecular genetic perspective. The objective of this review is to provide readers with a foundation of knowledge regarding the beige fats and a foundation for future research into the mechanisms of this process, which may lead to the development of new strategies for maintaining human health.

Adipose tissue is a crucial metabolic organ in the human body. It stores and exerts distinct physiological functions in different body regions. Fat not only serves as a cushion and insulator but also stores energy and conveys endocrine signals within the body. There is a growing recognition that adipose tissue is an organ that is misunderstood and underestimated in contribution to human health and disease progression by regulating its size and functionality. In mammals, the adipose tissue reservoir consists of three functionally distinct types of fat: white adipose tissue (WAT), brown adipose tissue (BAT), and beige or inducible brown adipose tissue (iWAT), which exhibits thermogenic capabilities intermediate between the other two. Fat in different depots exhibits considerable differences in origin, characteristics, and functions. They vary not only in adipocyte lineage, properties, thermogenesis, and endocrine functions but also in their immunological functions. In a recent study published in Nature Metabolism, Zhang et al. investigated the role of JunB in the thermogenic capacity of adipocytes and its significance in obesity and metabolic disorders. The study revealed that JunB expression in BAT coexists with both low and high thermogenic adipocytes, indicating a fundamental feature of heterogeneity and plasticity within BAT. In summary, this article demonstrates that research targeting JunB holds promise for improving diet-induced obesity and insulin resistance, offering new avenues for treating metabolic disorders.

Metabolically healthy obesity refers to obese individuals who do not develop metabolic disorders. These people store fat in subcutaneous adipose tissue (SAT) rather than in visceral adipose tissue (VAT). However, the molecules participating in this specific scenario remain elusive. Rab18, a lipid droplet (LD)-associated protein, mediates the contact between the endoplasmic reticulum (ER) and LDs to facilitate LD growth and maturation. In the present study, we show that the protein level of Rab18 is specifically upregulated in the SAT of obese people and mice. Rab18 adipocyte-specific knockout (Rab18 AKO) mice had a decreased volume ratio of SAT to VAT compared with wildtype mice. When subjected to high-fat diet (HFD), Rab18 AKO mice had increased ER stress and inflammation, reduced adiponectin, and decreased triacylglycerol (TAG) accumulation in SAT. In contrast, TAG accumulation in VAT, brown adipose tissue (BAT) or liver of Rab18 AKO mice had a moderate increase without ER stress stimulation. Rab18 AKO mice developed insulin resistance and systematic inflammation. Rab18 AKO mice maintained body temperature in response to acute and chronic cold induction with a thermogenic SAT, similar to the counterpart mice. Furthermore, Rab18-deficient 3T3-L1 adipocytes were more prone to palmitate-induced ER stress, indicating the involvement of Rab18 in alleviating lipid toxicity. Rab18 AKO mice provide a good animal model to investigate metabolic disorders such as impaired SAT. In conclusion, our studies reveal that Rab18 is a key and specific regulator that maintains the proper functions of SAT by alleviating lipid-induced ER stress.

Deciphering lipid metabolism in white adipose tissue (WAT) depots during weight gain is important to understand the heterogeneity of WAT and its roles in obesity. Here, we examined the expression of key enzymes of lipid metabolism and changes in the morphology of representative visceral (epididymal) and subcutaneous (inguinal) WAT (eWAT and iWAT, respectively)-in adult male rats acclimated to cold (4 ± 1 °C) for 45 days and reacclimated to room temperature (RT, 22 ± 1 °C) for 1, 3, 7, 12, 21, or 45 days. The relative mass of both depots decreased to a similar extent after cold acclimation. However, fatty acid synthase (FAS), glucose-6-phosphate dehydrogenase (G6PDH), and medium-chain acyl-CoA dehydrogenase (ACADM) protein level increased only in eWAT, whereas adipose triglyceride lipase (ATGL) expression increased only in iWAT. During reacclimation, the relative mass of eWAT reached control values on day 12 and that of iWAT on day 45 of reacclimation. The faster recovery of eWAT mass is associated with higher expression of FAS, acetyl-CoA carboxylase (ACC), G6PDH, and ACADM during reacclimation and a delayed increase in ATGL. The absence of an increase in proliferating cell nuclear antigen suggests that the observed depot-specific mass increase is predominantly due to metabolic adjustments. In summary, this study shows a differential rate of visceral and subcutaneous adipose tissue weight regain during post-cold reacclimation of rats at RT. Faster recovery of the visceral WAT as compared to subcutaneous WAT during reacclimation at RT could be attributed to observed differences in the expression patterns of lipid metabolic enzymes.

Hypertension, a prevalent global cardiovascular disease, affects approximately 45.4 % of adults worldwide. Despite advances in therapy, hypertension continues to pose a significant health risk due to inadequate management. It has been established that excessive adiposity contributes majorly to hypertension, accounting for 65 to 75 % of primary cases. Fat depots can be categorised into subcutaneous and visceral adipose tissue based on anatomical and physiological characteristics. The metabolic impact and the risk of hypertension are determined more significantly by visceral fat. Perirenal adipose tissue (PRAT), a viscera enveloping the kidney, is known for its superior vascularisation and abundant innervation. Although traditionally deemed as a mechanical support tissue, recent studies have indicated its contributing potential to hypertension. Hypertensive patients tend to have increased PRAT thickness compared to those without, and there is a positive correlation between PRAT thickness and elevated systolic blood pressure. This review encapsulates the anatomical characteristics and biogenesis of PRAT. We provide an overview of the potential mechanisms where PRAT may modulate blood pressure, including physical compression, paracrine effects, and neurogenic regulation. PRAT has become a promising target for hypertension management, and continuous effort is required to further explore the underlying mechanisms.

Epicardial adipose tissue (eAT) is a metabolically active fat depot that has been associated with a wide array of cardiac homeostatic functions and cardiometabolic diseases. A full understanding of its diverse physiological and pathological roles is hindered by the dearth of animal models. Here, we show, in the heart of an ectothermic teleost, the zebrafish, the existence of a fat depot localized underneath the epicardium, originating from the epicardium and exhibiting the molecular signature of beige adipocytes. Moreover, a subset of adipocytes within this cardiac fat tissue exhibits primitive thermogenic potential. Transcriptomic profiling and cross-species analysis revealed elevated glycolytic and cardiac homeostatic gene expression with downregulated obesity and inflammatory hallmarks in the teleost eAT compared to that of lean aged humans. Our findings unveil epicardium-derived beige fat in the heart of an ectotherm considered to possess solely white adipocytes for energy storage and identify pathways that may underlie age-driven remodeling of human eAT.

Adipose organ, historically known as specialized lipid-handling tissue serving as the long-term fat depot, is now appreciated as the largest endocrine organ composed of two main compartments, i.e., subcutaneous and visceral adipose tissue (AT), madding up white and beige/brown adipocytes. Adipose organ dysfunction manifested as maldistribution of the compartments, hypertrophic, hypoxic, inflamed, and insulin-resistant AT, contributes to the development of type 2 diabetes (T2D). Here, we highlight the role of nitric oxide (NO·) in AT (dys)function in relation to developing T2D. The key aspects determining lipid and glucose homeostasis in AT depend on the physiological levels of the NO· produced via endothelial NO· synthases (eNOS). In addition to decreased NO· bioavailability (via decreased expression/activity of eNOS or scavenging NO·), excessive NO· produced by inducible NOS (iNOS) in response to hypoxia and AT inflammation may be a critical interfering factor diverting NO· signaling to the formation of reactive oxygen and nitrogen species, resulting in AT and whole-body metabolic dysfunction. Pharmacological approaches boosting AT-NO· availability at physiological levels (by increasing NO· production and its stability), as well as suppression of iNOS-NO· synthesis, are potential candidates for developing NO·-based therapeutics in T2D.

Antipsychotic drug (APD) medication can lead to metabolic dysfunctions and weight gain, which together increase morbidity and mortality. Metabolically active visceral adipose tissue (VAT) in particular plays a crucial role in the etiopathology of these metabolic dysregulations. Here, we studied the effect of 12 weeks of drug medication by daily oral feeding of clozapine and haloperidol on the perirenal fat tissue as part of VAT of male and female Sprague Dawley rats in the context of complex former investigations on brain, liver, and blood. Adipocyte area values were determined, as well as triglycerides, non-esterified fatty acids (NEFAs), glucose, glycogen, lactate, malondialdehyde equivalents, ferric iron and protein levels of Perilipin-A, hormone-sensitive-lipase (HSL), hepcidin, glucose transporter-4 (Glut-4) and insulin receptor-ß (IR-ß). We found increased adipocyte mass in males, with slightly higher adipocyte area values in both males and females under clozapine treatment. Triglycerides, NEFAs, glucose and oxidative stress in the medicated groups were unchanged or slightly decreased. In contrast to controls and haloperidol-medicated rats, perirenal adipocyte mass and serum leptin levels were not correlated under clozapine. Protein expressions of perilipin-A, Glut-4 and HSL were decreased under clozapine treatment. IR-ß expression changed sex-specifically in the clozapine-medicated groups associated with higher hepcidin levels in the perirenal adipose tissue of clozapine-treated females. Taken together, clozapine and haloperidol had a smaller effect than expected on perirenal adipose tissue. The perirenal adipose tissue shows only weak changes in lipid and glucose metabolism. The main changes can be seen in the proteins examined, and probably in their effect on liver metabolism.

Perirenal fat is a pad that fills the retroperitoneal space outside the kidney, which affects kidney function in various ways. However, the association between perirenal fat and IgA nephropathy (IgAN) has not yet been elucidated. This study aimed to investigate the role of perirenal fat in predicting IgAN progression.

A total of 473 patients with biopsy-proven IgAN and follow-up information were recruited, and perirenal fat thickness (PFT) was measured using color Doppler ultrasonography at renal biopsy. Patients were divided into two groups according to the median PFT: the low-PFT group (PFT ≤1.34 cm, n = 239) and the high PFT group (PFT >1.35 cm, n = 234). A total of 473 healthy participants were included in the control group. Basic clinical characteristics were assessed at the time of renal biopsy, and the relationship between PFT and combined endpoints was analyzed. The renal composite endpoints were defined as a two-fold increase in blood creatinine level, end-stage renal disease (dialysis over 3 months). Kaplan-Meier survival analysis was used to explore the role of PFT in the progression of IgAN. Three clinicopathological models of multivariate Cox regression analysis were established to evaluate the association between PFT and renal prognosis in patients with IgAN.

Compared to healthy subjects, patients with IgAN showed significantly higher PFT. After a median follow-up of 50 months, 75 of 473 patients (15.9%) with IgAN reached renal composite endpoints. Among those, 13 of 239 patients (5.4%) were in the low PFT group, and 62 of 234 patients (26.5%) were in the high PFT group (p < 0.001). The results of three Cox regression models (including demographics, pathological and clinical indicators, and PFT) demonstrated that a higher PFT was significantly associated with a higher risk of reaching renal composite endpoints in patients with IgAN.

This study indicated a positive relationship between PFT at renal biopsy and renal progression in patients with IgAN, suggesting that perirenal fat might act as a marker of poor prognosis in patients with IgAN.

Diabetic kidney disease (DKD) is a significant healthcare burden worldwide that substantially increases the risk of kidney failure and cardiovascular events. To reduce the prevalence of DKD, extensive research is being conducted to determine the risk factors and consequently implement early interventions. Patients with type 2 diabetes mellitus (T2DM) are more likely to be obese. Abdominal adiposity is associated with a greater risk of kidney damage than general obesity. Abdominal adipose tissue can be divided into different fat depots according to the location and function, including visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), perirenal adipose tissue (PAT), and renal sinus adipose tissue (RSAT), which can be accurately measured by radiology techniques, such as computed tomography (CT) and magnetic resonance imaging (MRI). Abdominal fat depots may affect the development of DKD through different mechanisms, and radiologic abdominal adipose characteristics may serve as imaging indicators of DKD risk. This review will first describe the CT/MRI-based assessment of abdominal adipose depots and subsequently describe the current studies on abdominal adipose tissue and DKD development, as well as the underlying mechanisms in patients of T2DM with DKD.

One of the major global health and welfare issues is the treatment of obesity and associated metabolic disorders, such as type 2 diabetes mellitus and nonalcoholic fatty liver disease. Obesity, caused by the excessive accumulation of triglycerides in adipose tissues, induces adipocyte dysfunction, followed by inflammation, in adipose tissues and lipotoxicity in nonadipose tissues. Several studies have shown that obesity and glucose homeostasis are influenced by sphingolipid mediators, including ceramide and sphingosine 1-phosphate (S1P). Cellular accumulation of ceramide impairs pancreatic β-cell survival, confers insulin resistance in the liver and the skeletal muscle, and deteriorates adipose tissue inflammation via unknown molecular mechanisms. The roles of S1P are more complicated, because there are five cell-surface S1P receptors (S1PRs: S1P1-5) which have altered functions, different cellular expression patterns, and inapparent intracellular targets. Recent findings, including those by our group, support the notable concept that the pharmacological activation of S1P1 or S1P3 improves obesity and associated metabolic disorders, whereas that of S1P2 has the opposite effect. In addition, the regulation of S1P production by sphingosine kinase (SphK) is an essential factor affecting glucose homeostasis. This review summarizes the current knowledge on SphK/S1P/S1PR signaling in and against obesity, insulin resistance, and associated disorders.

The adipose tissue organ is organised as distinct anatomical depots located all along the body axis, and it is constituted of three different types of adipocytes: white, beige and brown, which are integrated with vascular, immune, neural, and extracellular stroma cells. These distinct adipocytes serve different specialised functions. The main function of white adipocytes is to ensure healthy storage of excess nutrients/energy and its rapid mobilisation to supply the demand of energy imposed by physiological cues in other organs, whereas brown and beige adipocytes are designed for heat production through uncoupling lipid oxidation from energy production. The concerted action of the three types of adipocytes/tissues ensures an optimal metabolic status. However, when one or several of these adipose depots become dysfunctional because of sustained lipid/nutrient overload, then insulin resistance and associated metabolic complications ensue. These metabolic alterations close a vicious cycle that negatively affects the adipose tissue functionality and compromises global metabolic homeostasis. Optimising white adipose tissue expandability and ensuring its functional metabolic flexibility and/or promoting brown/beige mediated thermogenic activity are complementary strategies that counteract obesity and its associated lipotoxic metabolic effects. However, the development of these therapeutic approaches requires a deep understanding of adipose tissue in all broad aspects. In this chapter, we will discuss the characteristics of the different adipose tissue depots with respect to origins and precursors recruitment, plasticity, cellular composition, and expandability capacity potential as well as molecular and metabolic characteristic signatures in both physiological and pathophysiological conditions. Current antilipotoxic strategies for future clinical application are also discussed in this chapter.

Metabolic diseases, featured with dysregulated energy homeostasis, have become major global health challenges. Patients with metabolic diseases have high probability to manifest multiple complications in lipid metabolism, e.g. obesity, insulin resistance and fatty liver. Therefore, targeting the hub genes in lipid metabolism may systemically ameliorate the metabolic diseases, along with the complications. Stearoyl-CoA desaturase 1(SCD1) is a key enzyme that desaturates the saturated fatty acids (SFAs) derived from de novo lipogenesis or diet to generate monounsaturated fatty acids (MUFAs). SCD1 maintains the metabolic and tissue homeostasis by responding to, and integrating the multiple layers of endogenous stimuli, which is mediated by the synthesized MUFAs. It critically regulates a myriad of physiological processes, including energy homeostasis, development, autophagy, tumorigenesis and inflammation. Aberrant transcriptional and epigenetic activation of SCD1 regulates AMPK/ACC, SIRT1/PGC1α, NcDase/Wnt, etc, and causes aberrant lipid accumulation, thereby promoting the progression of obesity, non-alcoholic fatty liver, diabetes and cancer. This review critically assesses the integrative mechanisms of the (patho)physiological functions of SCD1 in metabolic homeostasis, inflammation and autophagy. For translational perspective, potent SCD1 inhibitors have been developed to treat various types of cancer. We thus discuss the multidisciplinary advances that greatly accelerate the development of SCD1 new inhibitors. In conclusion, besides cancer treatment, SCD1 may serve as the promising target to combat multiple metabolic complications simultaneously.

Obesity is the leading risk factor for the development of type 2 diabetes and cardiovascular diseases. Childhood obesity represents an alarming health challenge because children with obesity are prone to remain with obesity throughout their life and have an increased morbidity and mortality risk. The ability of adipose tissue to store lipids and expand in size during excessive calorie intake is its most remarkable characteristic. Cellular and lipid turnovers determine adipose tissue size and are closely related with metabolic status. The mechanisms through which adipose tissue expands and how this affects systemic metabolic homeostasis are still poorly characterized. Furthermore, the mechanism through which increased adiposity extends from childhood to adulthood and its implications in metabolic health are in most part, still unknown. More studies on adipose tissue development in healthy and children with obesity are urgently needed. In the present review, we summarize the dynamics of white adipose tissue, from developmental origins to the mechanisms that allows it to grow and expand throughout lifetime and during obesity in children and in different mouse models used to address this largely unknown field. Specially, highlighting the role that excessive adiposity during the early life has on future's adipose tissue dynamics and individual's health.

Regardless of its anatomical site, adipose tissue shares a common energy-storage role but exhibits distinctive properties. Exploring the cellular and molecular heterogeneity of white adipose tissue (WAT) is crucial for comprehending its function and properties. However, existing single-nucleus RNA sequencing (snRNA-seq) studies of adipose tissue heterogeneity have examined only one or two depots. In this study, we employed snRNA-seq to test five representative depots including inguinal, epididymal, mesenteric, perirenal, and pericardial adipose tissues in mice under physiological conditions. By analyzing the contents of main cell categories and gene profiles of various depots, we identified their distinctive physiological properties. Immune cells and fibro-adipogenic progenitor cells (FAPs) showed dramatic differences among WAT depots, while adipocytes seemed to be conserved. The heightened presence of regulatory macrophages and B cells in pericardial adipose tissues implied their potential contribution to the preservation of coronary vascular function. Moreover, the selective aggregation of pericytes within mesenteric adipose tissue was likely associated with the maintenance of intestinal barrier homeostasis. Using a combination of RNA sequencing and snRNA-seq analysis, the major subpopulations of FAPs derived from these depots determined the site characteristics of FAPs to a certain extent. Our work establishes a systematic and reliable foundation for investigating the heterogeneity of WAT depots and elucidating the unique roles these depots play in coordinating the function of adjacent organs.